Table 2 The list of MCDA criteria

1.

Indication uniqueness

a) one unique indication (2 points),

b) more than one orphan indications (1 point),

c) one or more indications for common disease (0 points)

2.

Disease rarity

a) prevalence < 0,5 per 10,000 UE citizens (2 points),

b) prevalence in the range of 0,5 and 1 per 10,000 UE citizens (1 point),

c) prevalence >1 per 10,000 UE citizens (0 points)

3.

Disease severity

a) high mortality often with poor prognosis e.g. cancers (2 points)

b) chronic without high mortality and morbidity (1 point),

c) severe invalidity, severely harm of capacities central to individuals’ functioning in society – e.g. hearing, eyesight etc. (1 point)

4.

Advancement of technology

a) Advanced therapy medicinal product (ATMP) including biopharmaceutical, innovative synthetic entities and delivery systems as well non-biological complex drug (2 points),

b) conventional small molecule (molecular weight, MW < 500 Da) with at least one stereogenic (chiral) center in its structure (1 point),

c) widely available simple chemical entities (e.g. zinc acetate) including molecules easily synthesized from commercially available precursors - fine chemicals – (0 points)

5.

Manufacturing technology complexity

a) expensive biotechnological processes (2 points)

b) complex synthetic path consisting of at least three independent chemical transformations (1 point)

c) manufacturing require the use of separation techniques for most intermediates (1 point)

6.

Therapeutic alternative (unmet medical need)

a) no comparable alternative available (2 points)

b) second line treatment available (1 point)

c) at least one comparable alternative available (0 points)

7.

Scientific evidence for clinical efficiency (level of uncertainty)

a) randomised placebo(or active)-controlled clinical trial(s) (RCT) with hard endpoints such as overall survival or time to progression (TTP) (2 points),

b) randomised placebo(or active)-controlled clinical trial(s) (RCT) with surrogate endpoints (1 points),

c) uncontrolled non-randomised clinical trial(s), observation studies or cohort studies with relevant but only limited level of uncertainty (1 point),

d) very limited data with high level of uncertainty – e.g. case reports (0 points)

8.

Benefits from use of medicine (safety and adverse effects)

a) Only minor and reversible adverse events (2 points)

b) Low incidence of severe of adverse events (1 point)

c) High incidence of severe of adverse events (0 point)

9.

Cost effectiveness

a) ICER below 24 k€ (2 points)

b) ICER in the range between 24 k€ and 48 k€ (1 point)

c) ICER above 48 k€ (0 points)

10.

Budget impact (in €)

Total costs of reimbursement in first two years:

a) budget savings or positive budget impact below 1,2 M€ (2 points)

b) in the range between 1,2 and 2,4 M€ (1 point)

c) above 2,4 M€ (0 points)